This is a proposal requesting Phase III support for five years to continue our successful COBRE Center for Protease Research (CPR) at North Dakota State University (NDSU), which was established in 2001 with Phase I of grant P20RR15566. The overarching goal for the Center is to obtain fundamental understanding of the role of proteases in disease in the broadest sense. During the first ten years, the Center has funded twenty-seven faculty researchers and established two core facilities. Several of these faculty members have received major research funding awards from NIH and NSF (R01, CAREER, and Presidential Young Investigator Awards) and the majority of the junior faculty have successfully competed for NIH (R03, R15, and R21), American Heart Association, or Department of Defense grants. In total, the Center PIs have received more than $17,500,000 in new funding and an additional $1,000,000 in education grants. The PIs from the Center have published 335 peer-reviewed publications since 2001. The strategic plan for Phase III of the CPR COBRE Center during the next five years is (1) to maintain and strengthen the state-of-the-art Core Biology and Core Synthesis Facilities established during Phases I and II that are essential for the support of the research projects in the Center, (2) to support research pilot projects and training components to sustain a collaborative, multidisciplinary research environment, (3) to provide significant mentoring in professional activities for the development of junior faculty members, and (4) to maintain an administrative core that will be required to coordinate and evaluate the entire program, including the Pilot Project Program and the two research cores. In this application, the Center for Protease Research is requesting funds to continue its support of two core facilities, to establish a new Pilot Project Program for biomedical research, and an Administrative Core to coordinate these activities. NDSU has clearly recognized the tremendous resources the Center brings to bear on its continued development as a research-intensive university. Over the course of the requested Phase III grant, NDSU will contribute $1,250,000 in direct support of the Center. PUBLIC HEALTH RELEVANCE (provided by applicant): All of the research projects supported by our Center are directed toward obtaining a fundamental understanding of the role of proteases in disease. Successful outcome of these activities should lead to improved treatments of human diseases such as cancer, asthma, and diabetes.